Cell-free DNA as a potential biomarker for acute myocardial infarction: A systematic review and meta-analysis.

Background: Tissue necrosis releases cell-free deoxyribonucleic acid (cfDNA), leading to rapid increases in plasma concentration with clearance independent of kidney function. Aim: To explore the diagnostic role of cfDNA in acute myocardial infarction (AMI). Methods: This systematic review and meta-analysis included studies of cfDNA in patients with AMI and a comparator group without AMI. The quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool was used, with AMI determined from the criteria of the original study. Standardised mean differences (SMD) were obtained using a random-effects inverse variance model. Heterogeneity was reported as I2. Pooled sensitivity and specificity were computed using a bivariate model. The area under the curve (AUC) was estimated from a hierarchical summary receiver operating characteristics curve. Results: Seventeen studies were identified involving 1804 patients (n = 819 in the AMI group, n = 985 in the comparator group). Circulating cfDNA concentrations were greater in the AMI group (SMD 3.47 (95%CI: 2.54-4.41, p < 0.001)). The studies were of variable methodological quality with substantial heterogeneity (I2 = 98%, p < 0.001), possibly due to the differences in cfDNA quantification methodologies (Chi2 25.16, p < 0.001, I2 = 92%). Diagnostic accuracy was determined using six studies (n = 804), which yielded a sensitivity of 87% (95%CI: 72%-95%) and specificity of 96% (95%CI: 92%-98%). The AUC was 0.96 (95%CI: 0.93-0.98). Two studies reported a relationship between peak cfDNA and peak troponin. No studies reported data for patients with pre-existing kidney impairment. Conclusion: Plasma cfDNA appears to be a reliable biomarker of myocardial injury. Inferences from existing results are limited owing to methodology heterogeneity.

Higher versus lower enteral calorie delivery and gastrointestinal dysfunction in critical illness: A systematic review and meta-analysis.

BACKGROUND AND AIMS: In critical illness, enteral nutrition (EN) is frequently limited by gastrointestinal (GI) dysfunction. The aim of this systematic review and meta-analysis was to determine relationships between enteral calorie delivery and GI dysfunction in critically ill adults. METHODS: MEDLINE, EMCARE, EMBASE, and CINAHL databases were searched from 1 January 2000 to 11 August 2021 to identify parallel group randomised controlled trials of an EN intervention that resulted in a significant difference in calorie delivery between groups and reported at least one outcome relating to GI dysfunction. Study groups were categorised as 'higher' or 'lower' calorie delivery and data were extracted on study interventions, GI dysfunction and clinical outcomes. Extracted data were aggregated using a random effects model and presented as risk ratio with 95% confidence intervals. A P-value <0.05 was considered significant. The risk of publication bias was assessed graphically using a funnel plot. RESULTS: From 13 studies involving 6824 patients the mean calorie delivery in the higher calorie group was 1673 ± 468 kcal/day compared to 1121 ± 312 kcal/day in the lower calorie group. The higher calorie group had an increased risk of a large (any volume ≥300 ml) gastric residual volume (GRV) (RR 1.40; 95% CI 1.09, 1.80; P = 0.009) and prokinetic administration (RR 1.18; 95% CI 1.11, 1.27; P < 0.00001). There were no between group differences in the presence of vomiting/regurgitation (RR 0.93; 95% CI 0.58, 1.49; P = 0.76), diarrhoea (RR 1.12; 95% CI 0.93, 1.35; P = 0.22) or abdominal distension (RR 0.71; 95% CI 0.49, 1.04; P = 0.08). There was no evidence of publication bias. CONCLUSION: Higher calorie delivery is associated with increased rates of GRV≥300 ml and prokinetic administration, but not vomiting/regurgitation, diarrhoea or abdominal distension. OTHER: No funding was received for the conduct of this systematic review and meta-analysis. The protocol was prospectively registered with PROSPERO (CRD42021268876).

Perioperative outcomes and survival in elderly patients aged ≥ 75 years undergoing gastrectomy for gastric cancer: an 18-year retrospective analysis in a single Western centre.

PURPOSE: Surgical resection for elderly patients with gastric cancer is controversial. This study aims to evaluate the preoperative features and postoperative short- and long-term outcomes of elderly patients following surgical resection for gastric adenocarcinoma. METHODS: Between January 2000 and May 2018, a total of 177 consecutive patients underwent curative gastrectomy for gastric adenocarcinoma was retrospectively reviewed. Propensity score matching (PSM) analysis was used to balance confounding covariates between the elderly and non-elderly groups. Clinicopathological characteristics, intraoperative characteristics, postoperative complications and long-term survival outcomes including overall survival (OS) and Disease Specific Survival (DSS) were compared and analysed using the Kaplan-Meier log-rank test. Multivariate cox proportional hazards regression analysis of clinicopathological factors influencing survival were evaluated. RESULTS: There were 50 patients in the elderly group (age ≥ 75 years) and 127 patients in the non-elderly group (age < 75 years). Elderly patients had more comorbid conditions (p < 0.001), lower albumin concentration (p = 0.034), lower haemoglobin levels (p = 0.001), and poorer renal function (p = 0.043). TNM stage was similar between both groups (p = 0.174); however, lymphatic invasion (p = 0.006) and lymph node metastasis (p = 0.029) were higher in the elderly group. Elderly patients were much less likely to receive any chemo- (p < 0.001) or radiotherapy treatment (p = 0.007) with surgical treatment. After PSM, there were 50 patients in each group. Elderly patients were more likely to develop complications (Clavien Dindo ≥ 2: 50% vs. 26%, p = 0.003). The most common postoperative complications were pneumonia (12% vs. 6%, p = 0.498) and delirium (10% vs. 0%, p = 0.066). Elderly patients had a longer median length of hospital stay (median (IQR): 15.6(9.5) vs. 11.3 (9.9), p = 0.030). There were no differences in 30-day mortality (elderly vs. non-elderly: 1% vs. 1%, p = 0.988). Before and after PSM, age remains an independent predictor of postoperative complications. Before PSM, the estimated mean OS for the elderly and non-elderly patients were 108 months (95%CI, 72.5-143.5) and 143 months (95%CI, 123.0-163.8), respectively (p = 0.264). After PSM, the estimated mean OS for the elderly and non-elderly patients were 108 months (95%CI, 72.5-143.5) and 140 months (95%CI, 112.1-168.2), respectively, (p = 0.360). Before PSM, the estimated mean DSS for the elderly and non-elderly patients were 94 months (95%CI, 61.9-127.5) and 121 months (95%CI, 100.9-141.0), respectively (p = 0.405). After PSM, the estimated mean DSS for the elderly and non-elderly patients were 94 months (95%CI, 61.9-127.5) and 115 months (95%CI, 87.3-143.3), respectively (p = 0.721). Age was not an independent predictor of mortality following gastrectomy for gastric cancer in both PSM matched and unmatched cohort. CONCLUSION: Chronological age alone is not a contraindication to curative resection of gastric adenocarcinoma in elderly patients with acceptable risk. Whilst age affects perioperative complications, the incidence of postoperative mortality and overall survival were not significantly different between elderly and non-elderly gastric cancer patients treated with curative surgery. Gastrectomy with D2 lymphadenectomy can also be performed in carefully selected elderly patients by surgeons with expertise in gastric resection along with appropriate perioperative management.

Neuroprotective Properties of Vitamin C: A Scoping Review of Pre-Clinical and Clinical Studies.

There is a need for novel neuroprotective therapies. We aimed to review the evidence for exogenous vitamin C as a neuroprotective agent. MEDLINE, Embase, and Cochrane library databases were searched from inception to May 2020. Pre-clinical and clinical reports evaluating vitamin C for acute neurological injury were included. Twenty-two pre-clinical and 11 clinical studies were eligible for inclusion. Pre-clinical studies included models of traumatic and hypoxic brain injury, subarachnoid and intracerebral hemorrhage, and ischemic stroke. The median [IQR] maximum daily dose of vitamin C in animal studies was 120 [50-500] mg/kg. Twenty-one animal studies reported improvements in biomarkers, functional outcome, or both. Clinical studies included single reports in neonatal hypoxic encephalopathy, traumatic brain injury, and subarachnoid hemorrhage and eight studies in ischemic stroke. The median maximum daily dose of vitamin C was 750 [500-1000] mg, or ∼10 mg/kg for an average-size adult male. Apart from one case series of intracisternal vitamin C administration in subarachnoid hemorrhage, clinical studies reported no patient-centered benefit. Although pre-clinical trials suggest that exogenous vitamin C improves biomarkers of neuroprotection, functional outcome, and mortality, these results have not translated to humans. However, clinical trials used approximately one tenth of the vitamin C dose of animal studies.

Global Impact of Coronavirus Disease 2019 Infection Requiring Admission to the ICU: A Systematic Review and Meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented burden on the delivery of intensive care services worldwide. RESEARCH QUESTION: What is the global point estimate of deaths and risk factors for patients who are admitted to ICUs with severe COVID-19? STUDY DESIGN AND METHODS: In this systematic review and meta-analysis Medline, Embase, and the Cochrane library were searched up to August 1, 2020. Pooled prevalence of participant characteristics, clinical features, and outcome data was calculated with the use of random effects models. Subgroup analyses were based on geographic distribution, study type, quality assessment, sample size, end date, and patient disposition. Studies that reported in-hospital mortality rate of adult patients (age >18 years) with confirmed COVID-19 admitted to an ICU met study eligibility criteria. Critical evaluation was performed with the Newcastle Ottawa Scale for nonrandomized studies. RESULTS: Forty-five studies with 16,561 patients from 17 countries across four continents were included. Patients with COVID-19 who were admitted to ICUs had a mean age of 62.6 years (95% CI, 60.4-64.7). Common comorbidities included hypertension (49.5%; 95% CI, 44.9-54.0) and diabetes mellitus (26.6%; 95% CI, 22.7-30.8). More than three-quarters of cases experienced the development of ARDS (76.1%; 95% CI, 65.7-85.2). Invasive mechanical ventilation was required in 67.7% (95% CI, 59.1-75.7) of case, vasopressor support in 65.9% (95% CI, 52.4-78.4) of cases, renal replacement therapy in 16.9% (95% CI, 12.1-22.2) of cases, and extracorporeal membrane oxygenation in 6.4% (95% CI, 4.1-9.1) of cases. The duration of ICU and hospital admission was 10.8 days (95% CI, 9.3-18.4) and 19.1 days (95% CI, 16.3-21.9), respectively, with in-hospital mortality rate of 28.1% (95% CI, 23.4-33.0; I2 = 96%). No significant subgroup effect was observed. INTERPRETATION: Critically ill patients with COVID-19 who are admitted to the ICU require substantial organ support and prolonged ICU and hospital level care. The pooled estimate of global death from severe COVID-19 is <1 in 3.

Postoperative outcomes in elderly patients undergoing pancreatic resection for pancreatic adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer is a disease of the elderly. Surgical resection is usually offered to patients in early stage disease; however, pancreatic resection in the elderly is controversial. METHODS: MEDLINE, EMBASE and Cochrane Library, were searched for studies comparing short- and long-term outcomes of elderly (above the age of 70) with non-elderly patients (below the age of 70) following pancreatic resection for pancreatic adenocarcinoma over the period from the inception of electronic database to 2017. Twelve articles documenting 4860 patients were included. A meta-analysis of data on patient characteristics, operative techniques, and perioperative outcomes were analysed. Our primary endpoint was postoperative mortality, defined as 30-day mortality or in-hospitalisation mortality. RESULTS: There were 919 patients in the elderly group and 3941 patients in the non-elderly group. Elderly patients had worse ASA scores (p < 0.001) and more cardiovascular comorbidities (p = 0.002). Tumour size, T-stage, N-stage and tumour grade were similar between the elderly and non-elderly group (p > 0.05). Fewer elderly patients received a concomitant venous resection with their pancreatectomy (RR0.80, p = 0.003, I2 = 0%), achieved a negative margin status (RR0.76, p = 0.02, I2 = 28%) and underwent adjuvant chemotherapy treatment (RR0.69, p < 0.001, I2 = 42%). Overall complication (RR1.15, p < 0.001, I2 = 47%), in particular, respiratory complications (RR2.33, p = 0.004, I2 = 39%), was higher in the elderly group. There was no difference in postoperative pancreatic fistula formation, postoperative haemorrhage, intraabdominal abscess and length of hospital stay between both groups (p > 0.05). Postoperative mortality was similar between both groups (p = 0.17). Subgroup analysis according to the time of enrolment (<2000, ≥2000) showed a significant subgroup effect (Chi2 = 3.44, p = 0.06, I2 = 70.9%) and revealed that postoperative mortality in the elderly group improved over time (Before 2000: n = 1654, subtotal RR2.27, p = 0.02, I2 = 0%; From 2000 onwards: n = 3206, subtotal RR1.00, p = 0.99, I2 = 0%). CONCLUSION: Fewer elderly patients received chemotherapy and portal vein resection to achieve a clear margin. Pancreatic resection of pancreatic adenocarcinoma can be performed safely on elderly patients with acceptable risks in experienced centres by specialist hepatobiliary surgeons. Age alone should not be the only determinant for the selection of patients for surgical treatment of pancreatic adenocarcinoma.

A comparison of the operative outcomes of D1 and D2 gastrectomy performed at a single Western center with multiple surgeons: a retrospective analysis with propensity score matching.

BACKGROUND: There has been worldwide debate on lymphadenectomy for gastric cancer, with increasing consensus on performing an extended (D2) resection. There is a paucity of data in Australia. Our aim is to compare overall outcomes between a D1 and D2 lymphadenectomy for gastric cancer in a single specialist unit. METHODS: We performed a retrospective analysis on patients who underwent a curative primary gastric resection for gastric adenocarcinoma between January 1996 and April 2016, primary outcomes included overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) analysis was used to balance covariates between D1/D1+ and D2 groups. Kaplan-Meier survival curves of D1/D1+ versus D2 were constructed and evaluated using the log-rank test with subgroup analyses for pathological node (pN) status. Multiple Cox proportional hazards model was used to determine predictors of overall survival. RESULTS: Two hundred four patients underwent a gastrectomy, 54 had D1/D1+, and 150 had a D2 lymphadenectomy. After PSM, there were 39 patients in each group, the 10-year OS for D1/D1+ was 52.1 and 76.2% for D2 (p = 0.008), and 10-year DFS was 35% for D1 and 58.1% for D2 (p = 0.058). Subgroup analysis showed that node-negative (N0) patients had improved 5-year OS for D2 (90.9%), compared to D1/D1+ (76.4%) (p = 0.028). There was no difference in operative mortality between the groups (D1 vs D2: 2 vs 0%, p = 0.314), nor in post-operative complications (p = 0.227). Multiple Cox analysis showed advanced tumor stage (stages III and IV), and lymphadenectomy type (D1) and the presence of postoperative complications were independent predictors of poor overall survival. CONCLUSIONS: D2 lymphadenectomy with spleen and pancreas preservation can be performed safely on patients with gastric adenocarcinoma. Significant improvement in overall survival is observed in patients with N0 disease who underwent D2 lymphadenectomy without increasing operative morbidity or mortality. This paper supports the notion of a global consensus for a D2 lymphadenectomy, particularly in the Western context.